The objective of this project is to identify the tumor-produced agents responsible for the development of hypercalcemia in patients with neoplastic diseases who have no evidence of skeletal metastases, referred to here as the syndrome of pseudohyperparathyroidism. All patients with hypercalcemia and neoplastic disease at the Los Angeles County/University of Southern California Medical Center will have skeletal surveys and technetium-polyphophonate bone scans to determine the presence of skeletal metastases. In patients without metastases measurements of serum parathyroid hormone (PTH),1, 25-dihydroxyvitamin D (1,25(OH) 2 vit. D), and prostaglandin E2 (PGE2) will be made. In patients with elevated serum PTH concentration selective venous catheterization of the vessels draining the parathyroid glands and other major organs will be done in order to assess the site or origin of the PTH. In patients with ectopic hyperparathyroidism as a cause of pseudohyperparathyroidism serum and tumor extracts will be evaluated by gel filtration and radioimmunoassay to determine the molecular species of PTH. In patients with elevated serum 1,25(OH)2 vit. D or PGE2 levels measurements of these substances will be made in tumor extracts. Tumor extracts will also be evaluated for hypercalcemia activity bioassay in parathyroidectomized mice, in intact chickens, and in an in vitro bone organ culture system. If the tumor extracts induce bone resorption in vitro but no etiologic factor can be demonstrated, the influence of tumor extracts on the binding of PTH and 1,25(OH)2 vit. D to their specific receptors and on the production of prostaglandins by bone cells will be studied.